Nitric oxide (NO), a diatomic free radical produced endogenously by macrophages and other inflammatory cells, plays a key role in the natural immune response to pathogens. (Marletta, M. A., Tayeh, M. A., Hevel, J. M., Unraveling the biological significance of nitric oxide. Biofactors 1990, 2, 219-25; MacMicking, J.; Xie, Q. W.; Nathan, C., Nitric oxide and macrophage function. Annu. Rev. Immunol. 1997, 15, 323-350). Both NO and its reactive byproducts (e.g., peroxynitrite and dinitrogen trioxide) exert significant oxidative and nitrosative stress on bacterial cells to facilitate their killing. (Fang, F. C., Mechanisms of nitric oxide-related antimicrobial activity. J. Clin. Invest. 1997, 99, 2818-2825). Nitrosative stress acts to nitrosate thiols influencing protein and DNA function, while lipid peroxidation via oxidative stress destroys the bacterial membrane integrity. (Fang, 1997). Methods for delivering exogenous NO are thus actively being developed against both Gram-positive and Gram-negative bacteria. (Ghaffari, A., Miller, C. C., McMullin, B., Ghahary, A., Potential application of gaseous nitric oxide as a topical antimicrobial agent. Nitric Oxide-Biol. Chem. 2006, 14, 21-29; Hetrick, E. M., Shin, J. H., Stasko, N. A., Johnson, C. B., Wespe, D. A., Holmuhamedov, E., Schoenfisch, M. H., Bactericidal efficacy of nitric oxide-releasing silica nanoparticles. ACS Nano 2008, 2, 235-246; Privett, B. J., Deupree, S. M., Backlund, C. J., Rao, K. S., Johnson, C. B., Coneski, P. N., Schoenfisch, M. H., Synergy of Nitric Oxide and Silver Sulfadiazine against Gram-Negative, Gram-Positive, and Antibiotic-Resistant Pathogens. Mol. Pharm. 2010, 7, 2289-2296). While gaseous NO from a cylinder and NO delivered from small molecule NO donors have proven to be antimicrobial, (Hetrick, 2008; McMullin, B. B.; Chittock, D. R.; Roscoe, D. L.; Garcha, H.; Wang, L.; Miller, C. C., The antimicrobial effect of nitric oxide on the bacteria that cause nosocomial pneumonia in mechanically ventilated patients in the intensive care unit. Respir. Care 2005, 50, 1451-6) macromolecular scaffolds are more potent due to their ability to deliver large localized concentrations of NO. (Hetrick, 2008; Privett, 2010) The ability to achieve larger NO payloads and improved bactericidal efficacy using NO-releasing dendrimers and silica particles, relative to small molecule NO donors has been reported. (Hetrick, 2008; Shin, J. H., Metzger, S. K., Schoenfisch, M. H., Synthesis of nitric oxide-releasing silica nanoparticles. J. Am. Chem. Soc. 2007, 129, 4612-4619; Lu, Y., Sun, B., Li, C. H., Schoenfisch, M. H., Structurally Diverse Nitric Oxide-Releasing Poly(propylene imine) Dendrimers. Chem. Mater. 2011, 23, 4227-4233)
Bacterial infections are of concern. Bacteria typically exist in biofilms. Bacteria cause a large number of diseases and chronic illness with generalized symptoms, such as headache, nausea, vomiting, abdominal cramps, sore throat, sore eyes, and fever that may make an accurate diagnosis difficult.
The presently disclosed subject matter addresses, in whole or in part, these and other needs in the art.